Bonerama was formed in 1998 by trombone players Mark Mullins and Craig Klein, who, from 1990[1] up until late 2006, were also members of Harry Connick Jr.'s big band. Shortly thereafter, they added trombone players Steve Suter, Brian O'Neill, and Rick Trolsen, sousaphone player Charlie Kruger, guitarist Bert Cotton, and drummer Eric Bolivar. New Orleans drummers Russell Batiste, Stanton Moore, Doug Belote, Chad Gilmore, Terence Higgins, and Kevin O'Day have also been playing with Bonerama for periods of time. Later, Matt Perrine sousaphone replaced Charlie Kruger.

Bonerama trombonist Brian O'Neill had a heart attack and died while on a solo piano gig in New Orleans in December 2005.

Bonerama released their debut album in 2001, to positive reviews from OffBeat magazine, Gambit Weekly, and The Times Picayune. They had their first tour of the East Coast to sold-out venues. Rolling Stone editor, David Fricke, in his "On the Edge" column, wrote about them as "the ultimate in brass balls."

On January 2, 2008, Bonerama performed the national anthem at the 2008 Sugar Bowl. On February 5, they released a joint EP with OK Go, entitled You're Not Alone, to raise money for New Orleans musicians still displaced by the 2005 Hurricane Katrina. On February 11, 2008, Bonerama performed "A Million Ways" with Damian Kulash of OK Go on the Late Show with David Letterman.

After the departure of Rick Trolsen and Steve Suter in early 2009, trombonist Greg Hicks joined the band. In time, the three trombonists (Mullins, Klein and Hicks) became one of the most in-demand horn sections in New Orleans and began to appear under the name The Bonerama Horns. The Bonerama Horns appear on several songs on Alec Ounsworth's (Clap Your Hands Say Yeah) 2009 release Mo Beauty; R.E.M.'s 2010 release Collapse into Now (appearing on "It Happened Today" and "Oh My Heart"); and Sierra Leone Refugee All Stars 2010 release Rise and Shine.